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3H-noradrenaline and 3H-5-hydroxytryptamine release from rat brain slices and its presynaptic alpha-adrenergic modulation after long-term desipramine pretreatment

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Summary

The electrically-evoked release of 3H-noradrenaline from superfused cortex and hippocampus slices was strongly enhanced (by about 50%) after long-term (4 weeks) pretreatment with desipramine (10 mg/kg, twice daily). The release-enhancing effect of the α-receptor antagonist phentolamine was significantly reduced but the inhibitory effects of exogenous noradrenaline and clonidine on 3H-noradrenaline release were virtually unchanged after chronic desipramine treatment.

The K+-induced release of 3H-noradrenaline from superfused synaptosomes obtained from rats pretreated with desipramine was about 25% higher than that from synaptomes of control animals. However, noradrenaline inhibited the K+-induced synaptosomal 3H-noradrenaline release to the same extent (viz. by about 55%) in both cases.

The release of 3H-5-hydroxytryptamine induced by 26 mM K+ from cortex and hippocampus slices was not affected by chronic pretreatment with desipramine. In addition, no change was observed in the inhibitory effect of noradrenaline on 3H-5-hydroxytryptamine release.

It is concluded that long-term pretreatment with desipramine leads to selective changes in the basic mechanism(s) of noradrenaline release rather than to changes in the sensitivity of presynaptic α-adrenoceptors.

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  1. Department of Pharmacology, Free University, Medical Faculty, Van der Boechorststraat 7, NL-1081 BT, Amsterdam, The Netherlands

    Anton N. M. Schoffelmeer & Arie H. Mulder

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  1. Anton N. M. Schoffelmeer
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  2. Arie H. Mulder
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Schoffelmeer, A.N.M., Mulder, A.H. 3H-noradrenaline and 3H-5-hydroxytryptamine release from rat brain slices and its presynaptic alpha-adrenergic modulation after long-term desipramine pretreatment. Naunyn-Schmiedeberg's Arch. Pharmacol. 318, 173–180 (1982). https://doi.org/10.1007/BF00500477

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  • DOI: https://doi.org/10.1007/BF00500477

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